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1.
Mansfield C. Newson D.J. Birdsall P. Quayle J.A. Young R. MacBean M.D.A. Merrett R.P. 《Electronics letters》1991,27(18):1632-1633
Four-channel receiver arrays have been fabricated by monolithically integrating diffused InGaAs JFET-based electronics with InGaAs pin photodiodes. Cascode and simple inverter transimpedance amplifier circuits have been produced, both of which use a micro-FET as a tunable feedback element to vary bandwidth between 20 and 800 MHz. A sensitivity of -28.2 dBm was achieved at 1.25 Gbit/s with crosstalk between adjacent channels of -50 dB (electrical).<> 相似文献
2.
Thomas Janette A.; Arnold John R.P.; Basran Jaswir; Andrews Julie; Roberts Gordon C.K.; Birdsall Berry; Feeney James 《Protein engineering, design & selection : PEDS》1994,7(6):783-792
A mutant of Lactobacillus casei dihydrofolate reductase hasbeen constructed in which Thr63, a residue which interacts withthe 2'-phosphate group of the bound coenzyme, is replaced byalanine. This substitution does not affect kcat, but producesan 800-fold increase in the Km for NADPH, which reflects dissociationof NADPH from the enzyme-NADPH-tetrahydrofolate complex, anda 625-fold increase (corresponding to 3.8 kcal/mol) in the dissociationconstant for the enzyme-NADPH complex. The difference in magnitudeof these effects indicates a small effect of the substitutionon the negative cooperativity between NADPH and tetrahydrofolate.Stopped-flow studies of the kinetics of NADPH binding show thatthe weaker binding arises predominantly from a decrease in theassociation rate constant. NMR spectroscopy was used to comparethe structures of the mutant and wild-type enzymes in solution,in their complexes with methotrexate and with methotrexate andNADPH. This showed that only minimal structural changes resultfrom the mutation; a total of 47 residues were monitored fromtheir resolved 1H resonances, and of these nine in the binarycomplex and six in the ternary differed in chemical shift betweenmutant and wild-type enzyme. These affected residues are confinedto the immediate vicinity of residue 63. There is a substantialdifference in the 31P chemical shift of the 2'-phosphate ofthe bound coenzyme, reflecting the loss of the interaction withthe side chain of Thr63. The only changes in nuclear Overhausereffects (NOEs) observed were decreases in the intensity of NOEsbetween protons of the adenine ring of the bound coenzyme andthe nearby residues Leu62 and Ile102, showing that the substitutionof Thr63 does cause a change in the position or orientationof the adenine ring in its binding site. 相似文献
3.
WD Morgan B Birdsall VI Polshakov D Sali I Kompis J Feeney 《Canadian Metallurgical Quarterly》1995,34(37):11690-11702
Two-dimensional (2D) double-quantum-filtered correlation spectroscopy (DQF-COSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), and rotating-frame NOESY (ROESY) spectra were used to assign essentially all the protons in a 1:1 complex of Lactobacillus casei dihydrofolate reductase formed with an analogue of the antibacterial drug brodimoprim [2,4-diamino-5-(3',5'-dimethoxy-4'-bromobenzyl)pyrimidine]. The analogue has a 4,6-dicarboxylic acid side chain substituted on the 3'-O position designed to interact with the Arg 57 and His 28 residues in L. casei dihydrofolate reductase; it binds a factor of 10(3) more tightly to the enzyme than does the parent compound. Thirty-eight intermolecular and 11 intramolecular NOEs were measured involving the bound brodimoprim-4,6-dicarboxylic acid analogue. These provided the distance constraints used in conjunction with an energy minimization and simulated annealing protocol (using Discover from Biosym Ltd.) to dock the brodimoprim analogue into dihydrofolate reductase. In calculations where side chains and backbone fragments for binding-site residues were allowed flexibility, 90% of the 40 calculated structures had reasonable covalent geometry and none of them had NOE distance violations of greater than 0.36 A. The conformations of the aromatic rings in the bound ligand were well-defined in all the structures, with torsion angles tau 1 = -153 degrees +/- 4 degrees (C4-C5-C7-C1') and tau 2 = 53 degrees +/- 4 degrees (C5-C7-C1'-C2'): the aromatic rings of the ligand occupied essentially the same space in all the calculated structures (root mean square deviation value 1.83 A). Inclusion of the electrostatic interactions into the energy minimizations indicated that structures in which the 4,6-dicarboxylate group of the ligand interacts with the side chains of Arg 57 and His 28 are of low energy. Significant differences in side-chain and backbone conformations were detected between binding-site residues in the enzyme complexes with the brodimorpim analogue and methotrexate. 相似文献
4.
JA Court S Lloyd M Johnson M Griffiths NJ Birdsall MA Piggott AE Oakley PG Ince EK Perry RH Perry 《Canadian Metallurgical Quarterly》1997,101(1-2):93-105
High-affinity nicotine, alpha-bungarotoxin (alpha BT) and muscarinic receptor binding was measured in the human hippocampal formation in a series of 57 cases aged between 24 weeks gestation and 100 years. Changes in nicotine receptor binding during development and aging were more striking than differences in alpha BT and muscarinic binding. Nicotine binding was higher at the late foetal stage than at any other subsequent time in all areas investigated. In the hippocampus a fall in binding then occurred within the first six months of life, with little or no subsequent fall during aging, whereas in the entorhinal cortex and the presubiculum the major loss of nicotine binding occurred after the fourth decade. alpha BT binding was significantly elevated in the CA 1 region, but in no other region of the hippocampus, in the late foetus, and there was also a fall in alpha BT binding in the entorhinal cortex during aging from the second decade. The modest changes in total muscarinic binding, which appeared to reflect those in M1 and M3 + 4 rather than M2 binding, were a rise in the entorhinal cortex between the foetal stage and childhood and a tendency for receptors to fall with age in the hippocampus and subicular complex. These findings implicate mechanisms controlling the expression of nicotinic receptors to a greater extent than muscarinic receptors in postnatal development and aging in the human hippocampus. 相似文献
5.
6.
A single-state amplifier has been designed and fabricated using 0.25 mu m gate length, doped-channel HFET technology on InP substrates. Coplanar waveguide (CPW) was used for impedance matching. A gain of 14.4 dB was measured at 39 GHz.<> 相似文献
7.
Birdsall SA Dever PB Donovan JB Driscoll MM Lakin KM Pham TH 《IEEE transactions on ultrasonics, ferroelectrics, and frequency control》2002,49(5):643-648
Measurements of the static phase noise and vibration sensitivity of thin-film resonator (TFR) filters operating at 640 and 2110 MHz have been made. They show that the short-term frequency instability of the filters is small compared with that induced in the oscillator signal by the sustaining stage amplifier PM (phase modulation) noise. In-oscillator measurement of filter performance under vibration indicates that fractional frequency vibration sensitivities (δf 0/f0) are on the order of several parts in 10-9/g. Because the percentage bandwidth and order (number of poles) of the filters was fairly constant, so was the product of the center frequency and group delay. Thus, the fractional frequency vibration sensitivity of the filters can be expressed alternatively as carrier signal phase sensitivity to vibration. The τ-ω0 product for the filters that were tested was on the order of 300 rad, so that the equivalent phase sensitivity to vibration was approximately 1 grad/g 相似文献
8.
Birdsall DL; Huang W; Santi DV; Stroud RM; Finer-Moore J 《Protein engineering, design & selection : PEDS》1998,11(3):171-183
X-Ray crystal structures of Lactobacillus casei thymidylate synthase (TS)
mutant complexes of E60D with dUMP, and E60Q with dUMP or FdUMP, as well as
ternary complexes with folate analog inhibitor CB3717, are described. The
structures we report address the decrease in rate of formation of ternary
complexes in the E60 mutants. Structures of ternary complexes of L.casei TS
mimic ligand-bound TS just prior to covalent bond formation between ligands
and protein. Ternary complex structures of L.casei TS E60Q show the ligands
are not optimally aligned for making the necessary covalent bonds. Since
CB3717 is an analog of the open, activated form of the cofactor, these
structures suggest that the slow rate of ternary complex formation in E60
mutants is at least partly the result of impaired alignment of ligands in
the active site after binding and activation of the cofactor. Binary
complexes of TS E60Q and TS E60D with substrate (dUMP) show no change in
dUMP position or occupancy. These results are consistent with the fact that
Kd(dUMP) and Km(dUMP) are almost the same, and the rates of
folate-independent debromination of 5-bromo-dUMP are even higher than for
wild type TS.
相似文献
9.
Jimenez M.A.; Arnold J.R.P.; Andrews J.; Thomas J.A.; Roberts G.C.K.; Birdsall B.; Feeney J. 《Protein engineering, design & selection : PEDS》1989,2(8):627-631
The complex of Lactobacillus casei dihydrofolate reductase withthe substrate folate and the coenzyme NADP* has been shown toexist in solution as a mixture of three slowly interconvertingconformations whose proportions are pH-dependent and which differin the orientation of the pteridine ring of the substrate inthe binding site. The Asp26 Asn mutant of L. casei dihydrofolatereductase has been prepared by oligonucleotide-directed mutagenesisand studied by one-and two-dimensional 1H-NMR spectroscopy.NMR studies of the mutant enzymefolateNADP* complexshow that this exists to > 90% in a single conformation overthe pH* range 57.1. The single conformation observedcorresponds to conformation I (the methotrexate-likeconformation) of the wild-type enzymefolateNADP*complex. These observations demonstrate that Asp26 is the ionizablegroup controlling the pH-dependence of the conformational equilibriumseen in the wild-type enzyme. 相似文献
10.
Birdsall David L.; Finer-Moore Janet; Stroud Robert M. 《Protein engineering, design & selection : PEDS》2003,16(3):229-240
Cysteine is the only variant of D169, a cofactor-binding residuein thymidylate synthase, that shows in vivo activity. The 2.4Å crystal structure of Escherichia coli thymidylate synthaseD169C in a complex with dUMP and the antifolate CB3717 showsit to be an asymmetric dimer, with only one active site covalentlybonded to dUMP. At the active site with covalently bound substrate,C169 S 相似文献